Note that the cases mentioned in this article are extremely rare, literally 1 in a million.

With all that in mind, let’s get into the topic proper.

Introduction

In the 1980’s when HIV was first discovered, we needed a way to determine if a patient was infected with HIV or not.

Out of this need was born the first generation ELISA test which tested for the presence of HIV specific antibodies in the blood. Over the years, these ELISA tests became more and more accurate. However, they all depended on one thing: the assumption that a patient who is infected with HIV will develop antibodies to HIV so that it can be detected in the first place.

It was soon discovered that this was not always a valid assumption. There were instances where a person was infected with HIV but yet the ELISA test showed that he was not. This so called ‘False Negative’ ELISA test was initially blamed on the HIV Testing Window Period – the time from when a person is infected with HIV to when antibodies to HIV become detectable in the blood. However, we soon discovered that there were other, albeit extremely rare, causes of a False Negative HIV ELISA test.

The commonest cause of a False Negative ELISA – the testing Window Period

Initially, all cases of false positive ELISA tests were blamed on the testing window period. Till today, testing within the window period is still the commonest cause of a false negative ELISA.

The newer generation ELISAs can detect IgM antibodies which are produced much earlier than the IgG antibodies detected by older generation ELISA tests. This has significantly brought down the window period but it still hovers between 6 weeks to 3 months.

Newer tests including the P24 and RNA PCR has made the testing Window Period even shorter. Furthermore, these 2 tests are not dependent on the presence of antibodies and therefore will still be positive in people infected with HIV but do not develop antibodies (sero-negative infections).

Non-Clade B HIV virus

Once the issue with the testing window period was worked out, another problem arose.

As most tests were developed in North America and Europe, most of the focus was on detecting Clade B viruses which were the most commonly found subtype in these areas.

As such, some HIV ELISA tests that were developed were not so sensitive in detecting non-Clade B viruses.

This problem was quickly picked up and nowadays, HIV tests are all designed to detect non-Clade B viruses.

Hypogammaglobulinaemia, Agammaglobulinaemia

This is an extremely rare cause of sero-negative HIV infection (i.e. infected with HIV but with no detectable antibodies in the blood).

Hypogammaglobulinaemia in itself is a very rare condition in which patients have a (frequently genetically induced) inability to develop antibodies. It is rarer still to find such a patient and infected with HIV.

To date, I know of only 1 reported case in the NEJM in 2005.

Sero-reversion in End-Stage AIDS

We all know that HIV destroys the immune system and eventually leads to AIDS.

At the very late stages of AIDS, the patient’s immune system may be so poor that he/she is unable to produce antibodies anymore.

The antibodies that were present in the blood then disappear. This is what we call sero-reversion (the disappearance of antibodies) as opposed to sero-conversion (the appearance of antibodies).

Patients in these situations are always extremely ill and the diagnosis of a HIV infection is made by RNA PCR viral load test.

Interestingly enough, when some of these patients are given HAART, their immune system comes back to life and they start producing antibodies again, leading to sero-conversion and positive ELISA tests.

Sero-reversion with HAART

Many people also ask about and are worried about sero-reversion with HAART.

This is extremely rare. There are 2 known case reports of such a phenomenon. This refers to months on HAART and should not be confused with PEP. So far, there have been no case reports of delayed sero-conversion or sero-reversion with PEP.

HIV and Hepatitis C Co-Infection

Co-infection with Hepatitis C can prolong the HIV testing window period up to 12 months.

Unknown – Sero-Negative HIV Infections

There are a group of people in this world, albeit extremely rare, who seem apparently normal in all ways but just do not develop antibodies against HIV when infected with HIV.

These people often progress rapidly into AIDS and are only diagnosed when they are in AIDS stage.

It is theorized that the problem is with the patients rather than the virus. This is because a genetically identical virus in a different patient can illicit an antibody response. In other words, if the same virus infects 2 different people, one will develop antibodies against it and not the other.

It has been theorized that this has something to do with the HLA make up of a person which determines how his/her immune system works. But to date, we do not really know what causes these patients to remain persistently sero-negative.

Although such cases has been described, they are very rare. Less than 1 in a million of HIV cases diagnosed.

How do we overcome this problem?

That is the golden question.

Unfortunately, many of these patients present in late stage AIDS because their diagnosis of a HIV infection has been missed all this while.

The 2 solutions we have are:

P24 testing or Combo Test

These patients who do not develop antibodies against HIV will have a persistently high P24 level in their blood. So doing a P24 test will identify the infection.

This is very inline with the new HIV diagnostic testing Guidelines published in June 2014 by the US CDC which states that everyone should get a Combo test and not just an antibody test.

About Dr. TanDr. Tan graduated from the National University of Singapore in 2001. His residency was in the two largest public hospitals in Singapore; Tan Tock Seng Hospital and Singapore General Hospital.

I have three encounters with CSWs in China three years ago, and all happened within one month, with one back to back. All three encounters are unprotected, but no vaginal, oral, or anal sex took place. The first time CSW massaged me and give me a handjob, second time CSW massaged me and give me a breast sex with massage oil, thrid time massage and handjob with oil. One year ago, so two years after my exposures. I took an 4th gen Elisa (HIV 1/o/2 w/ reflexes). It came back non reactive next day morning. I do not have any identifiable risks after the encounters three years ago. I am a chronic marijuana smoker and probably smoked within 72 hours before test.

1.) Are these high risk exposures?
2.) Should I trust the results from my EIA 4th gen test?
3.) Is there any reason there could be a false negative two years after said exposures?
4.) Should I assume myself to be HIV negative despite symptoms?

hello doc, i had sex for the first time (unprotected vagina) last year which only lasted for 5 seconds with 2 thrust no ejaculation or vaginal fluid on my penis
with this brief exposure how likely am I to get hiv because have being dealing with some kind of symptoms and I’ve done more than 16 HIV test since the exposure last year september
the type of test used was alere determine 3rd generation HIV 1/2
should I go to a laboratory to conduct a standard test because I’m afraid the rapid test isn’t conclusive

I think I am hiv positive since 20 feb 2015 when i sex with a girl. because after 10 days i have fever,rash on neck,realised swollen lymph nodes,night sweats,cough, diahrea all the symptoms related to acute hiv I have suffered.After 3 month my BP was 135/86, my body weight increased because of over fat deposit in my body,always feeling tired,after 9 month was diagnosed with kidney stone,acid reflux desease.I have cooling sensation on leg and whole body. Muscle twitches of thigh,arm abdomen.pain all over body.In October 2016 i have a pain in my chest and heart i go for test my cholesterol is high. I do control on my diet and pain gone.but in January 2018 my heart beat is more than 120 at night and also chest pain and high bp. I have also pain in my hand and leg finger joint like arthritis. I go for test and I found my triglyceride was 240 and LDL was 125 HDL was 31 ,RBC .74 greater than normal, lymphocytes 17% Haemoglobin 16.5. platelets count 150. I think all the symptoms and problem that I suffer due to hiv then i decided to test and the HIV ANTIBODY SCREENING TEST come NEGATIVE , I don’t believe and I do another test for COMBO TEST ANTIBODY SCREENING TEST and P24 ANTIGEN TEST , ANTI HCV TEST and VDRL TEST for syphilis but all come Non reactive and negative. now what I do I believe it or not?
1- if i am not hiv positive then what cause my symptoms like arthritis,fatigue,low lymphocytes and low platelet
2- or my test is no conclusive because my lymphocytes is low they not produce enough antibody against hiv after 3 years ?
3-what I do now ?, which test i do for my symptoms?

I would consider your tests fully conclusive – no HIV. If you are still concerned about your symptoms, please see a doctor or visit us for a proper evaluation. We cannot make any diagnosis over the internet.

If there is a co-infection of Hep C with HIV, there may be delayed seroconversion and then it is recommended that the testing period be extended usually to about 6 months post-exposure. If you are tested negative after 6 months, then I would consider the results as conclusive.

I had lapdance with sex worker and my penis touch her penis for 5 sec (I didn’t penetrate)

I test here in the USA USING labcorp lab 4th gen test at 31 days post exposure it came out negative and today I did Oraquick at 74 days it came out negative
My question is :
– will the duo test at 31 days post exposure conclusive ( and what is the chance of false negative)
– what about the Oraquick at 74 days ( is it good news)
-my risk is my penis touch her anus but didn’t penetrate is it high risk ??????

Hi Dr.
went for a Lab test but wasn’t sure the kind of needle that was used on me, It’s been 4 months now went for Hiv1/2 antibody test came back negative,but am having oral thrush and lymph nodes for 4months now though it started when I took series of antibiotics injections and tablets.so do I consider the 4 months and 3days post exposure test conclusive?

hi dr i just go through the HEP C co-infection. i got an quick question, from the articles above, can the p24 antigen (Combo test) and PCR RNA test can overcome this issue? and furthermore is the combo test and pcr rna test result accuracy affected by the co-infection? thank you dr. i hope you can delete my fear as i nvr slp for few days after i read the articles but also see the false negative elisa test articles so wanna confirm with you guys. thanks

Hi dr jyst a question need your help. From the above. The hep c and hiv coinfection can be over come by using modern test such as combo test and rna pcr test? So is that mean the combo test at 28days or more exposure still conclusive for the false negative test on elisa? Include to overcome the hep c coinfection?

hi dr, sorry keep going ask question. but i really concern and scare after search some information about the test for hiv at the first place. however, i was go through all the material you guys provide. but there are few things would like to know. first of all, i was concerned on the co infection hep c and others. so may i know the modern test like 4th generation test able to detect it all? or hiv rna pcr test can over come that also? for your information,
1. i had rna pcr test at 10days after the post exposure (undetected)
2. i had done combo test at 28days from the post exposure (nonreactive),
3. i also conduct a test with the girl that i had protected sex with combo test at 27days also nonreactive.
can i know the is that conclusive for the both test including the test i conduct with the girl that i had protected sex at 27days post exposure? sorry dr all my test without any dr advice but i really need some help. thank and regards

HIV tests do NOT detect for Hep C infection. If you are concerned about Hep C infection, you should see a doctor for further evaluation. As for the rest of your questions, I have given the answers in your previous posts.

HIV RNA test is not recommended by CDC/WHO as a screening test for HIV. No, the 4th generation HIV test is limited if there is a co-infection with Hep C. Thus if you suspect there is a possibility of Hep C infection, you will need to be tested.

Thanks for this amazing service. A negative CMIA duo and HIV1 RNA PCR at 82 days post exposure 100% conclusive. Although, I have read your articles regarding the PCR RNA being conclusive for HIV1 at 10-12 days and a duo test being conclusive at 28 days for HIV1 and 3 months for HIV2. I ask this because I have a faint pain in both my underarms 5 weeks post exposure which still exists and is very bothersome. Please guide me. Thank you

I had a condom break with a Brazilian CSW. Exactly after 2 weeks I had fatigue,malaise,loss of appetite and started noticing rashes on my back.I also developed insomnia and had diarrhoea on a couple of days. I got tested with alere HIV combo test on day 18 and 26. Both of them came back negative. I then took two 4th gen ag/ab tests after 30 days. Both of them came back negative. After the tests on 30 days I got a rash on my shoulder which took 1 week to disappear.I also had low grade fever and sore throat for a couple of days which went away when I took dolonex dt tablet. I went to my doc at 6 weeks and he said results are good at 4 weeks. Do you think I should get tested again at 8 weeks ? If I have been having symptoms since 2 weeks would I not have turned up positive on the 30 day test ?

Hi,I have stopped taking trivenz tablets realising that I should have taken them within 48 hours, I have stopped taking them after 9 days and then developed itchy rash on my hands the following day.I have tested negative with Elisa Fourth generation after 14 and 21 days of exposure.Does rash caused by Trivenz tablets and how does it take to get of this medication from my body?

Hello,I had sex with a positive girl and condom broke on the 19 January 2018. I did hiv testing with Elisa Fourth generation as it can detect early hiv infection between 14 and 21 days, and results came back negative. Right now I’m developing itchy rash on my hands, Does it mean i’m positive?

Hi,
There is no specific symptoms that would indicate that you are infected with HIV. Also, it would be difficult to assess what the rash could be without examining you and doing tests if necessary. Please consult a doctor if you are still concern. If you like, you can please visit us for further evaluation (http://www.drtanandpartners.com/where-to-find-us/).

I had done sex with a girl.A unprotected sex with girl.After 24 days I had taken NAT screening (ID-NAT) result is NoT DETECTED for hiv1/2, HCV and HBV. So after 24 days of exposure test is conclusive can you please tell.
Does PCR and NAT are different? Test had been done through roche cobas t-scrn mpx .

I had sex exposure on January 16th.After 24 days I had taken ID-NAT (Individual donor nucleic acid test) which came as Not Dectected for all HIV 1/2,HBV,HCV. Can you please tell NAT is different from PCR? And also does my test is conclusive? Is it possible to become positive after 24 days?

Hello, I had sex with positive girl and and condom broke. I had diarrhea and muscle joint pain for two weeks. I test hiv with Elisa fourth generation and result came back negative. Should I consider results accurate and conclusive?

Hello, I had sex with positive girl,the condom broke but immediately notice it. I had diarrhea for two weeks then I decided to test hiv with Elisa fourth generation and it came back negative.i started taking forPEP after 20 days,if I test again should I consider results conclusive while talking PEP?

You should not be on PEP – it is not effective at 20 days post-exposure, only within 72 hours. So if there was HIV transmission, there is a risk of delayed test accuracy since you are on PEP. I would advise you to speak to your doctor for a proper assessment.

This page really gives an excellent information about seronegative cases. I know my following question is extremely stupid and extremely rare case.

1. I have a possible exposure 4 months back. I have got 4th gen DUO test after 4 months which checks for HIV1/2 antibodies and HIV1 antigen which turned out to be negative .

2. This test rules out every case of seronegativity mentioned in this page except this section “Unknown – Sero-Negative HIV Infections” in case of HIV 2 .

3. I have read an article where they mentioned in history there are only four cases which fits the description described in above section and all of them proceeded to AIDS stage within 6 months.

4. It does make sense because immune system does not react to HIV virus. And situation worsen quickly leading to faster aids stage.

5. I have read that viral load of HIV 2 does not grow as faster as HIV 1. considering this fact. Till now in this four months I did not get any symptom of HIV(no soar throat , rash or fever) but slight cold which did long for 4 weeks.

6. If I am in this category as described in “Unknown – Sero-Negative HIV Infections”. Don’t you think I would show at least one symptom of HIV 2 .

This is the last question which is stuck in my mind. Thanks for the help.

HAD PROTECTED SEX with call girl november 24 2017. 4 weeks later had sex with my fiancee no condom but she had negative rapdid test few months before. after 6 weeks after november call girl i had dry lip and abit sore. then i started itching but no rash or anythign i could see. The some stinging pains in between my legs in my groin and behind my knee which comes and goes but no swelling anywhere. There is nothing on my body and no fever any time. I worry about condom with the call girl in case she put a hole in it.I had negative rapid test and combo p24/antibody test last week after 9 weeks after the call girl and 4 weeks after my fiancee. But i still get some itching over my body and i cant see anything and my lip is a bit dry again. The tests were both negative. Is this ok at 9 weeks> or i need to test again at 12 weeks becauae of itching and dry lip and some stinging between legs and behind my kneww off and on?

Sir i met one aunty when i sucked her nipple some discharge entered into my mouth directly immediately i split out and i tested her same day and after 43 days with rapid test it is protected vaginal sex. Is any chances, please guide me sir

Sir i met one aunty when i sucked her nipple some discharge entered into my mouth directly immediately i split out and i tested her same day and after 43 days her status is negative and i had protected vaginal intrecourse with her after 20 days i tested with 4th generation elisa test it is negative i am so excited plz advice me sir

Hi is Ag/Ab HIV I/II (ELISA) is a COMBO or stand alone antibody test? It does mentioned Ag/Ab that is combo but mentioned (ELISA) too which is antibody test, so is a combo or just standalone antibody test?

Hello doctor, i was tested for hiv by an antigen/antibody combo test CMIA 7.5 weeks after possible exposure and it came back negative. But i still feel fatigued or tired after 2 to 3 hrs after waking up. Should i be worried of hepatitis c coinfection as the reason of a negative result?is it that easy for hepatitis c to be transmitted by sexual activity? How common is hepatitis c transmission by sexual activity? Or should i just move on with my negative result and not to worry anymore?…many thanks in advance doc..

hello dr,
I took a 4th gen combo test 25/26 days post exposure (anal sex w/prostitute with condom, i was drunk thou, so i can´t really be sure that the condom did´t break or if it slipped) 17-20 days later i began with a sore throat and a low grade fever 37,2-37,3. 6 weeks after i still have a little sore throat, also a bit of diarrea (2 days) lost about 5lb (i was so stressed that a
i could´t sleep or eat.)
on day 25/26 i took the combo Ac/ag. it came out negative.
knowing that the p24 antigen can be detected at about 14 days post exposure.
is this conclusive??????
thank you

Dr I had protected encounter on the 30th of November. I took 2 at home finger prick tests 14 days later which where negative and did a 4th gen Elisa which they said also checks for p24 at 19 days which also is negative. Should I re take the same test at day 21 and 28? And when can it be conclusive?

I had a risky contact on the 1st of October 2017 and tested on the 26th of November 2017, which is exactly 8 weeks after the exposure. The test type was ELISA, which was negative.

From the 14th of October i have been having general illness, such as sore throat, which subsided after 2 sets of antibiotics, however, i developed white patches at the very back of the throat, which are still there today even after taking 2 sets of antifungal medication.

I also had skin peeling on the hands, which subsided. There was no pain. The skin peeling then moved to the feet. It also almost gone there.

Currently feeling mild leg muscle pains (on and off).

Another woman sucked my penis on the 12th of November, now she has nausea and missed her period by 10 days, although a condom was correctly used on vaginal sex.

I had a p.24 combo test on day 16 and 18 which yielded a negative result. Checked really closely and no faint red line as well. I am now travelling at San Jose where is it pretty cold and i did not bring the adequete clothing so i have been out in the cold on and off.

Today is the 22nd day since the suspected infection and i have started to develop fever 37.5, alittle backache, coughing with green phlegm.

I would not be too worried, as a common cold is infinitely more likely than HIV infection. However, your tests are not yet conclusive so if you are still concerned, best to repeat a test at 28 days or later.

I had a RNA PCR done on 8th day and it was undetectable. I had then the combo test ( antibody + P24 antigen test) on 18th, 22nd and 28th day. All were non-reactive. I then also had an ELISA done on 31st day. It was also negative. Are my results conclusive? Can I move on now? Please advise.

Good Day sir! You have mentioned p24 antigen will remain positive entire life for seronegative people and I know is extremely rare and very unlikely. I need a little more understanding about p24.

1. If “I might say if” seroconversion(formation of antibodies) were to be delayed by ANY MEAN(any possible way such as HCV) the p24 still STAY DETECTABLE no matter how long it takes until antibodies were produced am I correct?

2. p24 antigen will NOT disappear by itself no matter how long it takes BUT releasing antibodies in the body will make it disappeared(UNDETECTABLE) am I correct?

3. Our body need to produce SUFFICIENT amount of antibodies to be detectable to make p24 antigen goes undetectable am I correct?

I have heard may said that P24 will disappears once antibodies are formed. If antibodies never develpo I mean persist “seronegative”, will P24 still present in blood for 4th generation test to up after few years for someone who do not develop antibodies? I mean not in late AIDS stage.

Hi Dr Tan I actually have a very confusing question. If let say a person antibody remain seronegative(No antibody develop) in HIV positive person will combo test become positive after many years since no antibody develop now can only rely on the P24 in combo test? I heard HIV antigen start to disappear for antibody develop case, what if no antibody is develop, will still P24 remain there for combo test to give a positive result after many years?

Hello sir..I tried to have anal sex with a woman..I don’t know her status..I put condom in my penis and poured coconut oil in her anus..I tried to insert inside her anus..but I cant..the condom teared..my penis was not inside her anus..is there any risk?? Also if my penis had a slight contact in her anus( for 2 sec) is there any risk..I had poured coconut oil..does it prevented me?..I’m confused.. please reply

Hello sir..I took HIV ab/ag combo test after 34 days post exposure (28 days I took pep)..on the same day I took RNA PCR qualitative test..they were all undetected…after 52 days post exposure (24 days post pep) I took Elisa which is non reactable..the result is test od: 0.045 and ref of: 0.201..result is non reactable..so can I start my normal life?? Stress is killing me